Statins protect mice from LPS-induced injury in a CD9-dependent manner.

<p>(<b>A</b>) WT mice were repeatedly intraperitoneally injected with vehicle (-) or 30 mg/kg fluvastatin (Fluv), and unchallenged (-) or intraperitoneally challenged with 30 mg/kg LPS (+). After 48 h, BMDMs were isolated and the level of CD9 was examined by immunoblotting. Anti-actin blots show that comparable amounts of protein were loaded in each lane. (<b>B</b>) WT mice were treated as in <b>A</b>. <i>CD9</i> mRNA levels in the BMDMs were examined by reverse transcription PCR. <i>GAPDH</i> is an internal loading control. (<b>C</b>) WT and CD9 KO mice were repeatedly intraperitoneally injected with vehicle (-) or 30 mg/kg fluvastatin (+), and intranasally challenged with 0.5 mg/kg LPS (+). After 24 h, activities of MMP-2 and MMP-9 in BALF were analyzed by gelatin zymography. (<b>D</b>) WT and CD9 KO mice were untreated (Cont, control) or intraperitoneally injected with vehicle or 20 mg/kg simvastatin (Simv) and intranasally challenged with 0.5 mg/kg LPS. After 4 days, total cells in BALF from the mice from each group (<i>n</i> = 9) were counted using a hemocytometer. Each bar represents the mean ± SEM. (<b>E</b>) WT and CD9 KO mice were treated as in <b>D</b>. Histological lung sections collected at 4 days were stained with hematoxylin and eosin. Scale bar, 100 µm. (<b>F</b>) WT and CD9 KO mice were intraperitoneally injected with vehicle or 20 mg/kg simvastatin, and intraperitoneally challenged with 40 mg/kg LPS. Survival of the mice from each group (<i>n</i> = 12) was monitored and analyzed by the Kaplan-Meier method. ^⋆<i>P</i> < 0.05; ^{⋆ ⋆}<i>P</i> < 0.01.